Having completed over a decade of work on antiviral treatment of genital herpes, we turned to studies of disease prevention. We completed an open 2 year phase 1 assessment of a new recombinant HSV-2 glycoprotein D vaccine in alum in 24 adults, some with and without prior HSV-1 and/or 2 infection. Vaccinations of 30 ug or 100 ug were given at 0, 1, 2, and 12 months and were associated with minimal local or systemic reactions. The vaccine induced excellent primary antibody in cellular immune responses and augmented preexisting humoral and cellular responses signicantly. We studied antibody and T cells from previously uninfected subjects and showed that the gD2 epitopes that the antibody and cells recognize correspond to those in genital herpes patients. On the basis of these excellent responses we enrolled 40 patients with recurrent gential herpes into a placebo-controlled vaccine trial in collaboration with the University of Washington. The goal is to determine whether boosted immunity leads to less frequent recurrences. The study was recently completed and the data are being examined. We have also begun to plan for further studies using gD2 and gB2 in the presence of potent new aadjuvant MF59.